This submission from the Children's Hospital of UPMC and the University of Pittsburgh responds to the TriaNet RFA DK-08-001. This group of investigators, with extensive experience who were a prior TrialNet center, has the resources, numerous recruited affilliates and a track record demonstrating their ability to continue TrialNet participation as a center. In order to answer the objective of the RFA, we propose a randomized controlled trial to evaluate the safety and efficacy of a new diabetes-suppressive cell vaccine, consisting of autologous monocyte-derived dendritic cells treated ex vivo with antisense phosphorothioate-modified oligonucleotides targeting the primary transcripts of the CD40, CD80 and CD86 co-stimulatory molecules (immunoregulatory DC; iDC). Phase 1 testing in patients with established Type 1 diabetes (T1D) and primates are almost completed. The hypotheses to be tested in this study are that gene-engineered autologous DC can attenuate or suppress the autoimmunity in: a) newly-diagnosed T1D, sparing residual beta cell mass, with restoration of insulin secretion as assessed by stimulated C-peptide levels, b) first degree relatives with disease predicting islet autoantibodies, to sustain insulin secretion assessed by stimulated C-peptide levels and to prevent progression to clinical T1D. Currently, other than immune suppression with considerable potential side effects, there is no other means to reverse or prevent new-onset T1D. These studies will be the first ever to employ autologous dendritic cell transfer to suppress an autoimmune disease and to possibly reverse it early in the clinical process. The strength of this proposal is the expertise and experience of the investigators,well established collaborations across centers and a novel intervention strategy